Increased activity of group II phospholipase A2 in plasma in rat sodium deoxycholate induced acute pancreatitis.

BACKGROUND: Two different types of secretory phospholipase A2 (PLA2), pancreatic group I (PLA2-I) and non-pancreatic group II (PLA2-II), have been identified and postulated to be associated with the pathogenesis of various diseases, such as acute pancreatitis, septic shock, and multiple organ failure. AIMS: To investigate the type of secretory PLA2 responsible for its catalytic activity found in plasma and ascites of experimental acute pancreatitis. METHODS: Acute pancreatitis of differing severity was induced by the injection of different concentrations (1% or 10%) of sodium deoxycholate (DCA) into the common biliopancreatic duct in rats, and catalytic PLA2 activity in plasma and ascites were differentiated by anti-PLA2-I antibody and specific inhibitor of PLA2-II. Survival rate and plasma amylase, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were also measured. RESULTS: In 1% and 10% DCA induced acute pancreatitis, plasma amylase values as well as PLA2 activity in ascites were greatly increased. PLA2 activity in plasma was also notably increased in 10% DCA induced acute pancreatitis, but not in 1% DCA induced acute pancreatitis. PLA2-I specific polyclonal antibody significantly inhibited PLA2 activity in ascites but not that in plasma. In contrast, plasma PLA2 activity was completely suppressed by PLA2-II specific inhibitor. In addition, a high mortality (93% at five hours) and a significant increase in plasma AST and ALT were noted in 10% DCA induced pancreatitis. CONCLUSION: Ascites PLA2 activity is mainly derived from PLA2-I, whereas plasma PLA2 activity is mostly derived from PLA2-II in severe acute pancreatitis, suggesting that increased plasma PLA2-II activity might be implicated in hepatic failure arising after severe acute pancreatitis.

Plasma biochemistry values of young beagle dogs.

Plasma components of 6 to 12-month-old beagles were examined using a Technicon auto-analyzer. Age-related changes were noted for 8 of the 21 components: the levels of total protein (T. Pro) and iron (Fe) gradually increased while those of alkaline phosphatase (ALP), creatine phosphokinase (CPK) and inorganic phosphorus (Pi) persistently decreased in both sexes. Triglyceride (Trigly) in female dogs, glutamic-pyruvic transaminase (GPT) and urea nitrogen (Urea-N) in male dogs tended to increase. The following thirteen components showed no significant variation during the period of observation: glucose (Glu), lactic dehydrogenase (LDH), albumin (Alb), creatinine (Crea), glutamic-oxaloacetic transaminase (GOT), leucine aminopeptidase (LAP), total bilirubin (T. Bil), amylase (Amy), total cholesterol (T. Chol), sodium (Na), potassium (K), chloride (Cl) and calcium (Ca). Our results generally agree with the reported findings on beagles from various institutions.

Species and sex differences in the inhibitory action of the corticosteroid alclometasone dipropionate on the hepatic drug-metabolizing system.

The effect of successive administration of the corticosteroid alclometasone dipropionate (ACM) on the hepatic drug-metabolizing system was examined using male and female rats. Although some pharmacological changes such as increases in plasma enzyme activity, lipid level and protein concentration appeared similarly in ACM-treated male and female rats, the activities of 7-alkoxycoumarin O-dealkylase, especially the O-depropylation activity, decreased dose-dependently by ACM administration only in male rats. ACM did not affect the hepatic drug-metabolizing activity in female rats and mice of both sexes. Also, ACM did not inhibit androgen-independent aniline hydroxylase activity even in male rats. The time course of changes of the drug-metabolizing system in male rats showed a rapid decrease in cytochrome P-450 content and O-depropylation activity following successive treatments with ACM, but there was a slow onset in the decreases of the O-demethylation and O-deethylation activities of 7-alkoxycoumarin. When ACM was withdrawn, the O-demethylation and O-deethylation activities rapidly returned to their control levels, while recovery of the O-depropylation activity was slow. These results suggested that ACM inhibits the hepatic drug-metabolizing enzyme activity associated with a specific form(s) of androgen-dependent cytochrome P-450 in male rats.

Lethal shock in partially hepatectomized rats administered tumor necrosis serum.

A minute dose of bacterial endotoxin is known to cause lethal shock in BCG (Bacillus Calmette Guérin)-sensitized mice and rats. To gain insight into the mechanism of this hypersensitivity to endotoxin, serum (tumor necrosis serum: TNS) was prepared from BCG-sensitized Lewis rats following endotoxin challenge and injected intravenously into Lewis rats 2 days after their partial hepatectomy. TNS injection caused lethal shock in Hpx (partially hepatectomized) rats but not in normally fed, fasted, or sham-operated rats. Hpx rats survived injection of serum prepared by either BCG sensitization or endotoxin challenge alone. Biochemical and histological examination of the Hpx rats injected with TNS indicated that profound hypoglycemia, hepatic and renal injury, and dysfunction of the coagulation system accompanied by hemorrhage were involved in the lethal shock. These experiments also suggested that serum component(s), probably monokine(s) derived from activated macrophages, might participate in the endotoxin shock in BCG-sensitized rats.